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At least 217 records · Page 12Linked to original sources
PubMed1986

Development and degeneration of retina in rds mutant mice: effects of light on the rate of degeneration in albino and pigmented homozygous and heterozygous mutant and normal mice.

The effect of light on the rate of visual cell loss in mice afflicted by the rds (retinal degeneration slow) gene was analyzed by comparing the changes in the thickness of the outer nuclear layer. Visual cell loss in the pigmented, homozygous mutant mice, maintained in cyclic light, is slightly slower than in the albino mutant mice. In the pigmented mutant mice, exposed to constant light, and in the albino mutant mice, reared in darkness, rate of cell loss is not significantly altered. In the albino animals exposed to constant light, the rate of cell loss is faster in the homozygous mutant than in the normal, and intermediate in the heterozygous mutant retina. The accelerated cell loss in the mutant retina progresses from the centre to the periphery, and affects the rods earlier than the cones. This resembles the photic lesion in the normal retina but is unlike the genetic lesion in the mutant retina which appears to progress from the periphery to the centre and affects both rods and cones. It is concluded that the visual cells in the retina of rds mutant mice are more vulnerable to photic damage than those in the retina of normal mice.

Albinism↗
PubMed2005

Production of transgenic and mutant mouse models.

Manipulation of the rodent genome by deliberately inserting (transgenic) or removing (knockout) a gene of interest or indeed by selectively breeding animals with a spontaneous or random mutation producing a trait of interest has been developed over several years. Mouse "fanciers" have been selectively breeding interesting mice since the turn of the last century to produce a plethora of different background strains of the common house mouse (Mus musculus). Rat (Rattus norvegicus) strain development has also proceeded with selective breeding, although the range of strains is more limited. The deliberate and targeted manipulation of the mouse genome has been with us for over two decades, with the rat genome a more recent addition, and yet this technology has been limited to a very narrow range of genes. With the complete mapping of the mouse genome (and the rat genome soon to follow), the powerful techniques of transgenic and knockout rodent production can be applied to the numerous genes whose expression is altered in existing stroke models.

Animals↗
PubMed1993

Altered isoactin gene expression in the affected bowel segments of the lethal spotted mouse.

BACKGROUND: Actin is a key contractile protein associated with the normal differentiation and function of gastrointestinal smooth muscle cells. Distinct changes in gastrointestinal smooth muscle cell morphology and function have been reported for the aganglionic rectum and megacolon of the adult lethal spotted mouse. This study examines what effect these changes in smooth muscle cell morphology and function have on the expression of the actin multigene family in both the aganglionic rectum and megacolon of the lethal spotted mouse. METHODS: Expression of the smooth muscle and cytoplasmic isoactins was examined by Northern blot analysis of the aganglionic rectum and megacolon of the homozygotic lethal spotted mouse and the equivalent bowel segments of control animals. RESULTS: The megacolon of the lethal spotted mouse showed a significant increase in gamma-smooth muscle isoactin expression. The aganglionic rectum of the lethal spotted mouse displayed a complex pattern of altered isoactin gene expression that included changes in both gamma-smooth muscle and beta-cytoplasmic isoactin expression. Strain-specific differences in the quantitative levels of isoactin gene expression were observed for the various bowel segments examined in this study. CONCLUSIONS: These results show that the changes in smooth muscle cell morphology and function observed in the lethal spotted mutant mouse are accompanied by significant alterations in isoactin gene expression.

Actins↗
PubMed1993

Restoration of early thymocyte differentiation in T-cell receptor beta-chain-deficient mutant mice by transmembrane signaling through CD3 epsilon.

Thymic repertoire selection requires the expression of the alpha beta CD3 T-cell receptor (TCR) together with the coreceptors CD4 and CD8. The appearance of CD4 and CD8 on thymocytes is the hallmark of a complex maturation step, accompanied by downregulation of the interleukin 2 receptor (IL-2R) alpha chain, arrest of rearrangement (i.e., allelic exclusion) of the TCR beta-chain locus, a burst of cell divisions, and reduction in cell size. This maturation step is inhibited in TCR beta-chain-deficient mouse strains and may depend on surface expression of an immature TCR complex containing CD3 and TCR beta chains but no TCR alpha chain. Here we show that the CD4+8+ double-positive (DP) stage can be induced by treatment of fetal thymic organ cultures with anti-CD3 epsilon monoclonal antibodies in several TCR beta-chain-deficient mouse strains: severe combined immunodeficient (scid) mice, mice carrying a mutation in the recombination activating gene 1 (Rag-1), or mice carrying a deletion in the TCR beta-chain locus itself. These findings suggest that CD3 epsilon is expressed on the thymocyte surface independent of and prior to the TCR beta chain. The data are consistent with the notion that in wild-type mice the DP stage is induced by transmembrane signaling through an immature CD3-TCR beta-chain complex, which can be bypassed by crosslinking of CD3 epsilon alone.

Animals↗
PubMed1984

Visually evoked eye movements in mouse mutants and inbred strains. A screening report.

The authors screened various inbred strains and mutants of the mouse, Mus musculus, for qualitatively abnormal or reduced numbers of optokinetic nystagmus (OKN) eye movements. Thirteen hypopigmentation mutants and ten neuromuscular mutants were found to have abnormal or markedly reduced OKN, but none of these mutants had retinal degeneration. Ten other hypopigmentation mutants and nine other neuromuscular mutants had relatively normal OKN, thus showing that neither hypopigmentation nor neuromuscular abnormality per se are well-correlated with abnormal OKN. These findings show that many mutants with visual defects are available from existing holdings. These visual mutants may serve as a resource for the study of the function and development of the mammalian visual system.

Animals↗
PubMed1996

Abrogation of c-kit/Steel factor-dependent tumorigenesis by kinase defective mutants of the c-kit receptor: c-kit kinase defective mutants as candidate tools for cancer gene therapy.

The growth and survival of many types of cancer cells are known to be supported by specific growth factor/cytokine systems. Among these, the activation of c-kit receptor and its ligand steel factor participates in several types of human carcinogenesis. W mutations of laboratory mouse strains are loss of functional mutations of the c-kit receptor. To examine the validity of these mutants in investigating c-kit-mediated carcinogenesis and in the treatment of c-kit-dependent tumors, we introduced various W mutations (W, Wv, and W42) into a transgenic mouse strain carrying human papillomavirus oncogenes, in which c-kit/Steel-mediated tumorigenesis occurs with a very high incidence. In all transgenic strains carrying a W mutation, the c-kit deficiency affected the tumorgenic process to various degrees. Tumor development was markedly suppressed in transgenic strains carrying kinase defective mutations (Wv and W42) in a heterozygous condition. In null-type (W) heterozygous transgenic mice, tumorigenesis was suppressed at a lower level. Moreover, minimal focal legions or, in some cases, no focal legions were found in the testes of W/Wv heterozygous transgenic mice, showing a close relationship between tumor cell growth and the degree of c-kit inactivation. These results indicated that c-kit activity is a pivotal determinant of testicular tumor development and that the kinase defective mutants of c-kit are valuable for treating c-kit-dependent cancer, as well as for clarifying the c-kit-mediated carcinogenesis.

Animals↗
PubMed1997

Mapping of the mouse Tdgf1 gene and Tdgf pseudogenes.

Teratocarcinoma-derived growth factor-1 (Tdgf1), a member of the "EGF family" of growth factors, is expressed during mouse gastrulation in the forming mesoderm and later in the truncus arteriosus of the developing heart. In humans, TDGF1 is highly expressed in germ cell tumors and in colon and mammary carcinomas. In mouse, one gene (Tdgf1) and two pseudogenes (Tdgf1-ps1 and Tdgf1-ps2) have been isolated and characterized. Tdgf1 corresponds to the gene expressed in F9 teratocarcinoma cells. Tdgf1-ps1 and Tdgf1-ps2 are two intronless sequences with all the characteristics of retroposons. In the present paper, we assign the chromosomal location for Tdgf1, Tdgf1-ps1, and Tdgf1-ps2 sequences to Chromosomes (Chrs) 9, 16, and 17, respectively. Two previously described mouse mutants, scant hair (sch) and fur deficient (fd), map near the Tdgf1 gene. Analysis of their DNA coding region provided no evidence that Tdgf1 could be the responsible gene for these phenotypes. Finally, analysis of the DNA from several Mus musculus strains and from Mus spretus mice revealed a highly variable restriction pattern and the absence of the Tdgf1-ps1 genomic sequence from the Mus spretus genome.

Animals↗
PubMed1985

Abnormal thyroid hormone binding to serum proteins in ob/ob and db/db genetically obese mice.

Sera from ob/ob and db/db genetically obese mice exhibited abnormal nonspecific (no antibody present) binding measurements in T4 and T3 RIAs employing dextran-charcoal separations. They also showed decreased charcoal uptake compared to sera of lean controls in a conventional charcoal T4 uptake binding test. After correction for the abnormal nonspecific binding and after extraction of serum, mean serum T4 concentrations were similar in control and ob/ob mice. Mean serum T3 concentrations differed significantly (85 ng/dl in controls and 178 ng/dl in ob/ob) when a correction for altered binding in the T3 assay was made, but not when extracted serum was assayed (109 ng/dl in lean and 124 ng/dl in ob/ob). Dialyzable fractions of T4 and T3 were significantly reduced in both ob/ob and db/db mice. Free T4 concentrations were 0.82 +/- 0.05 (+/- SE) ng/dl in control and 0.61 +/- 0.05 ng/dl in ob/ob sera (P less than 0.01). Polyacrylamide gel electrophoresis showed increased binding of tracer T4 and T3 in ob/ob and db/db sera to a postalbumin with mobility similar to that of human T4-binding globulin. In ob/ob sera, this appeared to result from an increased binding capacity of the postalbumin. After in vivo iv injection of tracer T4 and T3 to ob/ob and lean control mice, analysis of tissue and plasma radioactivity showed that, except for T4 in cerebral cortex, tissue to plasma T4 and T3 ratios were lower in cerebral cortex, cerebellum, and liver of ob/ob mice. In summary, these data show increased binding of T4 and T3 to a postalbumin in two strains of genetically obese mice and, in the ob/ob strain, complex relationships between tissue and serum concentrations of thyroid hormones.

Animals↗
PubMed1988

Herpes simplex virus type 1 infection in mice with severe combined immunodeficiency (SCID).

Herpes simplex virus type 1 (HSV-1) infection in mutant mice with severe combined immunodeficiency (SCID mice), i.e., mice in which the differentiation of both T and B lymphocytes is severely impaired, was studied. All control (infected and not treated with antibodies or with immune spleen cells) SCID mice were dead by 17 days after intracutaneous injection in the right midflank with 1 x 10(5) PFU of a virulent HSV-1 strain, Hayashida. Immunization with an avirulent strain of HSV-1 (SKa) did not protect them from death or prolong the survival time. Tissue virus titration of infected mice killed at various times after inoculation detected infectious virus in various organs, dorsal root ganglia, spinal cord, brain, kidney and adrenal gland in addition to the inoculation site of the skin in SCID mice, whereas virus could be detected only in the inoculation site and the nervous tissues in euthymic BALB/c mice, and in the adrenal gland from only one out of 17 nude mice. Human gamma globulin containing neutralizing antibody against HSV-1 prolonged the survival time but did not protect SCID mice from death. Transfer of spleen cells from immunized BALB/c mice protected the infected SCID mice from death. Treatment of spleen cells with anti-Thy 1.2 monoclonal antibody and complement abolished the protection.

Animals↗
PubMed1996

Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation.

Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cml+) exhibits profound spontaneous locomotor hyperactivity resulting from a deletion mutation. This deletion encompasses several genes including Snap, which encodes SNAP-25, a nerve terminal protein involved in neurotransmitter release. Administration of amphetamine, a drug that acts presynaptically, markedly reduced the locomotor activity in coloboma mice but increased the activity of control mice implicating presynaptic function in the behavioral abnormality. In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice. When a transgene encoding SNAP-25 was bred into the coloboma strain to complement the Snap deletion, the hyperactivity expressed by these mice was rescued, returning these corrected mice to normal levels of locomotor activity. These results demonstrate that the hyperactivity exhibited by these mice is the result of abnormalities in presynaptic function specifically attributable to deficits in SNAP-25 expression.

Amphetamine↗
PubMed1985

The optokinetic nystagmus and ocular pigmentation of hypopigmented mouse mutants.

We tested the optokinetic nystagmus (OKN) reflex of various hypopigmented mutant mice and ultrastructurally examined the pigmentation of various ocular structures in these mutants. Using electron microscopy we examined the pigmentation of the choroid and retinal pigment epithelium (RPE) and measured the numerical density, volume density, and distribution of RPE melanosomes of mice with the following phenotypes: (1) wild type, (2) mutants that have abnormal or no OKN in response to horizontally moving, full-field stimulation, and (3) other mutants that have normal OKN but reduced choroidal pigmentation. We also measured the OKN of all these mice in response to horizontally moving stimuli that were restricted to the nasal or to the temporal retina. We found that in the mutants with normal OKN the numerical density of melanosomes in the RPE was within the range found for wild type, while the numerical density was reduced for the mutants with abnormal OKN. For one mutant with normal RPE pigmentation and normal OKN, the choroidal pigmentation was nearly absent. For the genotypes with abnormal OKN the volume density of the RPE melanosomes and percent apical melanosomes were sometimes greater and sometimes less than normal. The OKN patterns of these mice fell into the following categories: (1) wild type; (2) field-restriction dependent OKN with small following movements but no OKN in response to full-field stimulation, normal OKN in response to stimulation of the nasal retina, and OKN of reversed direction in response to stimulation of the temporal retina; (3) oblique with slow oblique following movements and reduced numbers of OKNs with oblique quick phases in response to horizontally moving, full-field stimulation, nearly normal OKN in response to stimulation of the nasal retina, and OKN of reversed direction in response to stimulation of the temporal retina. The horizontal component of the oblique response to full-field stimulation was in the same direction for the two eyes, but the vertical component was in the opposite direction. (4) Slow, small amplitude, with no or very small following movements in response to full-field stimulation, following movements in response to stimulation of the nasal retina and reversed "following" movements in response to stimulation of the temporal retina but few or no quick phases of the OKN for any stimulus condition. These results show that a variety of abnormalities of the OKN occur for hypopigmentation mutants of the mouse.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The murine mutation jaundiced is caused by replacement of an arginine with a stop codon in the mRNA encoding the ninth repeat of beta-spectrin.

The jaundiced, ja/ja, mouse mutant has a severe hemolytic anemia associated with a deficiency of beta-spectrin in erythrocyte ghosts. Genes for the disease phenotype and beta-spectrin colocalize on Chromosome 12. beta-Spectrin mRNA is not detected in reticulocytes or in brain from newborn mutant mice. To locate the nucleotide sequence alteration, the erythroid beta-spectrin transcript from mutant spleen was amplified by reverse transcription PCR and sequenced. A C-to-T alteration is present in the mutant transcript and produces a premature stop codon from an arginine codon in mRNA encoding repeat 9 of beta-spectrin at amino acid position 1160. The point mutation introduces a Dde I site that is present in PCR-amplified DNA of ja/ja and ja/+ mice but not of +/+ control mice from the strain of origin, 129/Sv, or from the two strains, WB/Re and C57BL/6J, in which the mutation has been fixed by over 53 generations of backcrossing. The genetic data confirm that the point mutation is responsible for the severe reductions in beta-spectrin mRNA of jaundiced mice.

Amino Acid Sequence↗
PubMed1994

Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice.

Neural tube defects (NTD) in humans have been considered to have a multifactorial aetiology, however the participating genes have not been identified. The curly-tail (ct) mutant mouse develops NTD that resemble the human malformations in location, pathology and associated abnormalities. Moreover, there appears to be multifactorial influence on the incidence of NTD in offspring of curly-tail mice. We now describe a linkage analysis that localizes the ct gene to distal chromosome 4 in mice. Further analysis using recombinant inbred strains demonstrates the presence of at least three modifier loci that influence the incidence of NTD. This study provides definitive evidence for multifactorial inheritance in a mouse model of human NTD.

Abnormalities, Multiple↗